Spray device and method

ABSTRACT

A spray device including a barrel having a bypass and at least two spaced stoppers defining a first and second chambers and a spray nozzle. Movement of the first stopper drives the second stopper to the bypass and the fluid in the first chamber into the second chamber, mixing the fluid and substance. Continued movement of the first and second stoppers drives the mixture through the spray nozzle. The spray device may include a third stopper having a body in the tubular barrel which is moved toward the spray nozzle. The movement of the third stopper provides space for the mixture and prevents unpressurized fluid from flowing through the spray nozzle. The third stopper includes an axial stalk. The stalk may be deformable or the stalk may be separate from the body and the spray nozzle includes a longitudinal internal passage which provides communication with the spray port.

FIELD OF THE INVENTION

This invention relates to a spray device which may be utilized todeliver an spray of medicament, drug, vaccine or other substances to apatient for various applications including but not limited to therespiratory system including the mouth or ear of a patient or fortopical applications. More specifically, the spray device and method ofapplication of this invention may be utilized to mix a fluid medicament,diluent or solvent or other substance in liquid, powder or lyophilizedform and spray the mixture for application to a patient as described.

BACKGROUND OF THE INVENTION

Various spray devices have been developed by the applicant and otherswhich have been in use for many years. As used herein, the terms“substance” or “medical substance” are intended to broadly cover anyvaccine, drug, medicament or other substance which, when applied to apatient, results in the cure, alleviation, suspension, prevention,diagnosis or treatment of a disease or condition of the patient. Suchspray devices are commonly limited to a liquid medicament which isstored in a container having a spray head and a pump or the container isformed of a flexible polymer and the liquid is forced through the sprayhead by squeezing the container. Such spray devices are thereforelimited to liquid medicaments having a relatively long shelf life.Syringes with a sprayer have also been developed by the applicant asdisclosed in U.S. Pat. No. 5,601,077 assigned to the assignee of thepresent application.

It is also conventional to store medical substances in a sealed vial orother medical container for later use. Such medicaments may be in a dry,lyophilized (freeze-dried) or powder form to increase shelf life. Suchdry, lyophilized or powdered drugs are generally stored in a sealed vialand reconstituted in liquid form for administration to a patient byadding a diluent or solvent. There are also liquid medical substanceswhich are particularly efficacious if mixed prior to use, but themixture has a relatively short shelf life or liquid medical substanceswhich are not stable after mixing. Conventional medical vials forstoring medical substances are generally sealed with an elastomericstopper and a thin malleable metal cap, such as aluminum, encloses theopen end of the vial, which is generally crimped beneath the rim of thevial. A dry, lyophilized or powdered medical substance is normallyreconstituted by piercing the elastomeric stopper with the needlecannula of a syringe containing the diluent or solvent. Liquid drugs arealso mixed prior to use using a hypodermic syringe containing the secondliquid substance as described. This method of reconstituting a dry,lyophilized or powder substance or mixing liquid substances thereforerequires the use of several steps and manipulation by the patient orhealthcare worker including removal of the aluminum cap and the use of ahypodermic syringe having a sharp needle cannula is subject to potentialerror, contamination or injury. It would therefore be desirable andconvenient for a healthcare worker or patient to have a spray devicewhich mixes the liquid and medical substance, preferably at the time ofapplication and which eliminates the requirement for a syringe having asharp needle cannula.

It is also conventional to mix a liquid and a medical substance in asyringe prior to injection. Such syringes are generally referred to as“two-component syringe assemblies” and include a syringe barreltypically formed of glass having a needle cannula at one end, a bypassspaced from the needle cannula and the open end and a pair of spacedelastomeric stoppers in the syringe barrel spaced from the bypass asdisclosed, for example, in U.S. Pat. Nos. 4,599,082 and 5,899,881 bothassigned to the assignee of the present application. The chamber in thesyringe barrel defined between the stoppers is generally filled with aliquid and the chamber between the second stopper and the needle cannulamay contain a liquid, powder or lyophilized substance, whereby movementof the first stopper drives the second stopper to the bypass area andcontinued movement of the first stopper drives liquid through thebypass, mixing the liquid with the substance in the second chamber.However, this technology has not been applied or adapted for use in aspray device and prior art spray devices are not adapted for mixingfluid or powder substances at the time of application as set forthabove. There is, therefore, a need for a spray device, wherein themedical substance may be mixed in the device, preferably at or near thetime of the application of the spray to the patient.

SUMMARY OF THE INVENTION

In its broadest application, the spray device of this inventioncomprises a tubular body or barrel having first and second open ends, abypass between the open ends, a spray nozzle on the second open endhaving a spray nozzle port preferably coaxially aligned with the tubularbody, first and second spaced stoppers located between the first openend of the tubular body and the bypass, a fluid between the first andsecond stoppers and a medical substance between the second stopper andthe spray nozzle which may be a liquid, powder or lyophilized medicalsubstance. Thus, movement of the first stopper toward the second openend of the tubular body moves the second stopper to the bypass area,causing the fluid to flow between the second stopper and the spraynozzle mixing the fluid with the medical substance. Continued movementof the first stopper drives the first stopper against the second stopperand continued movement of the first stopper drives the mixture of fluidand medical substance through the spray nozzle creating a mist ofdroplets suitable for application to a patient. As described above, thespray device of this invention may be utilized for various applicationsincluding but not limited to delivery to the respiratory system of thepatient, topical applications and application of spray to the ear canal.As used herein, the term “respiratory system,” broadly covers the nasaland oral passages, lungs, etc.

The preferred embodiments of the spray device of this invention includea third stopper having an external diameter in sealed relation with theinternal surface of the tubular body or barrel initially located in thetubular barrel between the second stopper and the second open end of thetubular body, such that movement of the first and second stoppers movesthe third stopper into the spray nozzle providing space for mixing ofthe fluid and substance and expelling air through the spray port. In themost preferred embodiment of the spray device, the spray nozzle includesa body portion having a generally cylindrical internal surface includingan internal diameter generally equal to the internal surface of thetubular barrel. The internal surface of the body portion includes agenerally longitudinally extending internal passage establishing fluidcommunication between the tubular barrel and the spray nozzle port whenthe third stopper is located within the body portion of the spraynozzle. The preferred embodiments of the third stopper of the spraydevice of this invention further includes a longitudinally extendingaxial projection having a diameter less than the diameter of the bodyportion and the spray nozzle includes a central opening configured toreceive the longitudinal projection of the third stopper.

In one preferred embodiment, the longitudinal projection of the thirdstopper is resilient and the overall longitudinal length of the thirdstopper including the longitudinal projection is greater than thelongitudinal length of the body portion of the spray nozzle. In thisembodiment, the longitudinal projection of the third stopper isresiliently deformed against an internal surface of the central openingin the spray nozzle, such that the entire body portion of the thirdstopper is received in the body portion of the spray nozzle,establishing fluid communication between the tubular barrel and thespray nozzle port through the generally longitudinally extendinginternal groove. In another preferred embodiment, the internal surfaceof the central opening in the spray nozzle includes an annular ribadjacent the opening which sealingly engages an end portion of thelongitudinal projection and the longitudinal projection further includesa reduced diameter neck portion, such that axial deformation of thelongitudinal projection receives the annular rib in the reduced diameterneck portion of the longitudinal projection, establishing fluidcommunication around the longitudinal projection. In this embodiment, itis not necessary for the longitudinal length of the third stopper to beinitially greater than the longitudinal length of the spray nozzle.

In the other embodiments of the spray device of this invention, thelongitudinal projection of the third stopper is separate from the bodyportion and may be formed of a nonresilient polymer. In theseembodiments, the separate end portion of the third stopper is initiallyreceived in the central opening in the spray nozzle and the body portionof the third stopper is initially spaced from the end portion adjacentthe second open end of the tubular barrel, such that movement of thefirst and second stoppers drives the body portion of the third stopperinto the body portion of the spray nozzle and against the end portion,establishing fluid communication between the tubular barrel and thespray nozzle port through the generally longitudinally extendinginternal passage as described above.

Alternatively, the end portion of the third stopper having thelongitudinally extending projection may also include means to establishfluid communication through the body portion of the third stopper uponreceipt of the body portion of the third stopper in the body portion ofthe spray nozzle. In one embodiment, the third stopper includes anopening partially through the body portion of the third stopper and aseptum sealing the opening, wherein the separate end portion includes anaxially projecting piercing element or portion. In this embodiment,movement of the body portion of the third stopper toward the end portiondrives the piercing element through the septum, establishing fluidcommunication through the body portion of the third stopper. In anotherembodiment, the body portion of the third stopper includes a centralpassage therethrough and a sealing element, such as a ball in thepassage, and the separate end portion includes an axially projectingdriver portion configured to be received in the axial passage throughthe body portion, such that movement of the body portion of the thirdstopper into the body portion of the nozzle drives the driver portion ofthe end portion through the axial passage in the body portion of thestopper, removing the sealing element in the passage and establishingfluid communication through the passage.

The method of delivering a fine spray of a medical substance to apatient utilizing the spray device of this invention will now beunderstood from the description of the device above. In general, themethod of delivering a fine spray of medical substance to a patientincludes driving the first stopper in the tubular barrel adjacent thefirst open end of the barrel toward the second stopper until the secondstopper reaches the bypass area. The method of this invention thenincludes continuing to drive the first stopper toward the secondstopper, causing the fluid between the first and second stoppers to flowthrough the bypass and mix the fluid with the medical substance untilthe first stopper engages the second stopper. Finally, the method ofthis invention includes driving the first and second stoppers throughthe tubular barrel, causing the mixture to flow through the spraynozzle, thereby creating a fine mist of the mixture for application to apatient. As set forth above, the method of this invention may beutilized to deliver a fine mist of fluid for various applicationsincluding but not limited to delivery to the respiratory system of thepatient through the nose or mouth, topical applications and otherapplications including application of a spray to the ear canal forexample.

The method of delivering a fine spray of fluid to a patient utilizingthe preferred embodiments of the spray device described above furtherincludes driving or moving the first and second stoppers in the tubularbarrel toward the third stopper following mixing as described above. Thefluid pressure then drives the third stopper, or the body portion of thethird stopper where the end portion and body portion are separate,within the spray nozzle, establishing fluid communication between thetubular barrel and the spray nozzle as described above. Where thelongitudinal projection of the third stopper is integral with the bodyportion, as described above, the method of this invention then includesdriving the first and second stoppers toward the third stopper. Thefluid pressure then drives the longitudinal projection of the thirdstopper into the central opening in the spray nozzle, deforming thelongitudinal projection axially to establish fluid communication betweenthe tubular barrel and the spray nozzle port as described above.

Alternatively, where the end portion of the third stopper is separatefrom the body portion and the longitudinal projection of the end portionis initially received in the central opening in the spray nozzle and thebody portion is initially spaced from the end portion in the tubularbarrel, the method of this invention includes driving the first andsecond stoppers toward the third stopper, which drives the body portionof the third stopper into the body portion of the spray nozzle intocontact with the end portion, establishing fluid communication betweenthe tubular barrel and the spray nozzle port. In one embodiment, whereinthe body portion of the third stopper includes a pierceable septum andthe separate end portion of the third stopper includes a projectingpiercing element or projection, the method of this invention includespiercing the septum in the body portion of the third stopper toestablish fluid communication through the body portion of the thirdstopper. In the other alternative embodiment, wherein the body portionof the third stopper includes an axial passage having a sealing membersuch as a ball within the axial passage and the separate end portion ofthe third stopper includes an axially projecting driver portionconfigured to be received within the passage, the method of thisinvention includes driving the body portion of the third stopper towardthe separate end portion, which drives the axially projecting driverportion through the axial passage in the body portion, establishingfluid communication through the body portion of the third stopper.

The spray device and method of this invention therefore has severaladvantages over the prior methods of delivering a fine spray of amedical substance to a patient described above. First, the device andmethod of this invention requires only one container for two substanceswhich, as described above, may comprise a fluid, such as a liquidmedical substance, diluent or solvent, or a delivery gas, and the secondsubstance may be a liquid, powder or lyophilized medical substance.Another advantage of the spray apparatus and method of this invention isthat the substances can be filled from the opposed open ends of thetubular body or barrel, minimizing the risk of crosscontamination duringfilling as discussed further below.

The spray device and method of this invention also has safety benefitsas described above. First, reconstitution of a dry, powder orlyophilized medical substance or mixing of medical substances does notrequire use of a syringe or other device having a sharp needle cannula.Further, mixing the fluid and medical substance in the tubular barrelsignificantly reduced the number of manipulations and steps as comparedto the vial and syringe method of reconstituting a medical substanceresulting in better aseptic control, reduced error and risk ofadministration of an incomplete dosage. As will be understood, thetubular body or barrel may be formed of glass or a clear plastic suchthat the substances are visible before and after reconstitution.Further, as described below, the spray device of this invention mayutilize a cap which is received over the spray nozzle, which may bevented by providing discontinuous ribs, permitting movement of the thirdstopper without removing the cap. Other advantages and meritoriousfeatures of this invention will be understood from the followingdescription of the preferred embodiments, the appended claims and thedrawings, a brief description of which follows.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a side partially cross-sectioned view of one embodiment of thedual chamber spray device of this invention prior to actuation;

FIG. 2 is a side partially cross-sectioned view of the spray deviceshown in FIG. 1 following actuation and during mixing of the substances;

FIG. 3 is a side partially cross-sectioned view of the spray deviceshown in FIGS. 1 and 2 near completion of the spray sequence;

FIG. 4 is a side partially cross-sectioned view of a preferredalternative embodiment of the spray device of this invention prior toactuation;

FIG. 5 is a side partially cross-sectioned view of the spray deviceshown in FIG. 4 during actuation and mixing of the substances;

FIG. 6 is a side partially cross-sectioned view of the spray device inFIGS. 4 and 5 following mixing of the substances;

FIG. 7 is a partial side view partially cross-sectioned of the spraydevice in FIGS. 4 to 6 during spraying;

FIG. 8 is a partial side partially cross-sectioned view of the spraydevice similar to FIG. 7 following completion of the spray;

FIG. 9 is an exploded perspective view of the components of the spraydevice shown in FIGS. 4 to 8;

FIG. 10 is a side cross-sectioned perspective view of the spray nozzlein the spray device shown in FIGS. 4 to 9;

FIG. 11 is a side cross-sectioned perspective view of one embodiment ofthe end cap in the spray device shown in FIGS. 4, 5 and 9;

FIG. 12 is a partial side partially cross-sectioned view of analternative embodiment of the spray device of this invention duringactuation;

FIG. 13 is a partial side partially cross-sectioned view of theembodiment of the spray device shown in FIG. 12 near completion of thespray sequence;

FIG. 14 is a partial side partially cross-sectioned view of a furtheralternative embodiment of the spray device of this invention duringactuation;

FIG. 15 is a partial side partially cross-sectioned view of the spraydevice shown in FIG. 14 near completion of the spray sequence;

FIG. 16 is a partial side partially cross-sectioned view of a furtheralternative embodiment of the spray device of this invention duringactuation; and

FIG. 17 is a partial side partially cross-sectioned view of the spraydevice shown in FIG. 16 near completion of the spray sequence.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

As set forth above, the spray device of this invention combines theadvantages of a dual chamber or two-component syringe in a spray devicefor various spray applications of a medical substance, which eliminatesthe requirement of mixing the constituents of the substances using ahypodermic syringe or cartridge having a sharp needle cannula and a vialhaving an elastomeric stopper and malleable metal cap. The embodimentsof the spray device of this invention illustrated in the drawings anddescribed below provides mixing of substances in the body of the spraydevice and spray of a fine mist of medical substances for variousapplications including, but not limited to, the respiratory system ofthe patient through the nose or mouth, topical applications and otherapplications including, for example, applications through the patient'sear canal.

In the embodiment shown in FIGS. 1 to 3, the spray device 20 includes atubular body or barrel 22 having a generally cylindrical internalsurface 24, a reduced diameter tip portion 26 having a distal open end28 and a proximal open end 29. For the purposes of description only, the“proximal end” refers to the end of the device closest to the hand ofthe patient or healthcare worker holding the spray device and the“distal end” refers to the end furthest from the person holding thespray device. The tubular body or barrel 22 further includes a bypass 30in the form of a longitudinally enlarged portion or bulge having achannel 31 permitting passage of fluid through the bypass 30 asdescribed below. As stated below, the bypass 30 may have alternativeforms including internal ribs, etc.

The spray device 20 further includes a first stopper 32 adjacent theproximal open end 29 of the tubular body 22 and a second stopper 34spaced from the first stopper 32 and located between the proximal openend 29 and the bypass 30. In the disclosed embodiment, the secondstopper 34 is located in the tubular body 22 adjacent the bypass 30. Thestoppers 32 and 34 may be conventionally formed of a resilient orelastomeric material, such as rubber, synthetic rubber, plastic, etc.,and preferably include a plurality of spaced annular ribs 36 whichsealingly engage the internal cylindrical surface 24 of the tubularbarrel 22 as shown, but the stoppers 32 and 34 are moveable within thetubular barrel 22 as will be understood by those skilled in this art. Inthe disclosed embodiment, the proximal or first stopper 32 includes aconventional plunger 38 having a proximal flange portion 40, such thatthe user of the spray device 20 can drive the first stopper 32 towardthe distal or second stopper 34 as described further below. The plunger38 may be cruciform in shape as shown and may be formed integral withthe stopper 32, the end portion 38 may be threaded into the firststopper 32 (not shown) or otherwise secured as is conventional withhypodermic syringes. Alternatively, the spray device may be in the formof a cartridge, wherein the plunger 38 is replaced by a drive means (notshown) which drives the first stopper 32 toward the second stopper 34 asis conventional with medical cartridges. The first and second stoppers32 and 34 respectively divide the tubular body 22 into a first chamber42, between the first and second stoppers, and a second chamber 44between the second stopper 34 and the distal open end 28 of the tubularbarrel. As described below, the first chamber 42 is filled or partiallyfilled with a fluid, such as a liquid or a gas and the second chamber 44is at least partially filled with a liquid, powder or lyophilizedmedical substance which are mixed in the spray device 20 duringactuation of the device.

The spray nozzle and cap assembly 46 may be conventional for spraydevices of this type, such as the spray nozzle and cap assemblydisclosed in the above-referenced U.S. Pat. No. 5,601,077 assigned tothe assignee of the present invention. The spray nozzle and cap assembly46 disclosed in FIGS. 1 to 3 includes a cup-shaped cap 48, a tubularnozzle body 50 having a distal end portion 52 and a spray nozzle port 54preferably coaxially aligned with the longitudinal axis of thecylindrical internal surface 24 of the tubular barrel 22. The spraynozzle and cap assembly further includes a valve 56 located between thedistal open end 28 and the end portion 52 of the tubular nozzle body 50.As described more fully in the above-referenced U.S. Pat. No. 5,601,077,the valve 56 includes a cylindrical portion 58 coaxially aligned withthe spray nozzle port 54 and an annular skirt portion 60. The disclosedembodiment of the spray nozzle prevents unpressurized fluid in thetubular barrel 22 from flowing through the spray nozzle port 54 whileallowing fluid under pressure to flow distally through the spray nozzleport 54. The tubular nozzle body 50 in the disclosed embodiment isretained on the tip portion 26 of the tubular barrel 22 by aninterference fit, but may be attached by any suitable means includingbut not limited to threading, thermal welding, gluing, etc.

The operation of the two-chamber spray device 20 shown in FIGS. 1 to 3may now be described, as follows. First, the tubular barrel is at leastpartially filled with a substance suitable for mixing prior toapplication. The first chamber 42 between the first and second stoppers32 and 34, respectively, is filled with a fluid, which may be a fluidmedical substance, liquid solvent or diluent for the substance in thesecond chamber 44 or a delivery gas. Thus, the second chamber 44 may bepartially filled with a liquid or a powdered or lyophilized medicalsubstance as described above. The fluid in the first chamber 42 is thenmixed with the substance in the second chamber 44 by driving the firststopper 32 toward the second stopper 34 or toward the distal open end 28of the tubular barrel 22. In the disclosed embodiment, this isaccomplished by driving the plunger 38 into the tubular barrel 22 asshown by arrow 62 in FIG. 2. The fluid in the first chamber 42 thusdrives the second stopper 34 into the barrel opposite or facing thebypass 30 as shown in FIG. 2, wherein the fluid in the first chamber 42is driven through the passage 31 in the bypass 30 as shown by arrow 64in FIG. 2, wherein the fluid in the chamber 42 is mixed with thesubstance in the second chamber 44. The cap 48 may be removed prior toactuation of the spray device 20 as shown in FIG. 2 or the cap mayinclude air passages as described below in regard to FIG. 11. The firststopper 32 then engages the second stopper 34 driving the mixture in thesecond chamber through the second or distal open end 28 of the tubularbarrel or body 22 as shown by arrows 66 in FIG. 3 forming a fine sprayor mist of droplets 68 as shown in FIG. 3. During actuation of the spraydevice 20, the mixed fluid received in the tubular nozzle body 50 underpressure through the distal open end 28 of the tubular barrel deformsthe annular skirt portion 60 which is formed of a resilient materialsuch as natural or synthetic rubber, or plastic, permitting the fluid toflow through the nozzle body 50 to the spray nozzle port 54, generatingthe fine spray 68.

A preferred embodiment of the spray device 120 shown in FIGS. 4 to 11will now be described. The spray device 120 includes a tubular body orbarrel 122 having a generally cylindrical internal surface 124, a distalopen end 128 and a proximal open end 129. In this embodiment of thespray device 120, the proximal open end 129 of the tubular body 122 hasa cylindrical internal surface 124 having the same diameter as thedistal open end 128. For ease of description, like elements of the spraydevice 120 is numbered in the same sequence as the spray device 20 shownin FIGS. 1 to 3. The tubular body or barrel 122 also includes a bypass130 having a passage or channel 131 as described above in regard to thespray device 20 shown in FIGS. 1 to 3.

The spray device further includes a proximal or first stopper 132adjacent the proximal open end 129 and a second stopper 134 spaced fromthe first stopper 132 and located in the tubular barrel 122 between thefirst stopper 132 and the bypass 130. As described above in regard toFIGS. 1 to 3, the stoppers 132 and 134 may be formed of a resilientmaterial, such as natural or synthetic rubber, plastic, etc., andpreferably includes a plurality of spaced annular ribs 136 whichsealingly engage the cylindrical internal surface 124 of the tubularbarrel 122. The first stopper 132 may include a plunger 138 fixed to orintegrally formed with the first stopper 132. Alternatively, the plunger138 may be replaced with a conventional drive means such asconventionally used with medical cartridge as described above. Theplunger may be cruciform in cross-section and may include a flange 140for driving the first plunger through the tubular barrel 122.

In the preferred embodiment of the spray device 120 shown in FIGS. 4 to11 and the remaining figures, the spray device includes a third stopper170 located between the bypass 130 and the open distal end 128 of thetubular barrel 122. The third stopper 170 is preferably locatedgenerally adjacent the open distal end 128 of the tubular barrel 122 andinitially located within the tubular barrel 122. The third stopper 170may also be formed of a resilient plastic or elastomeric material, andin the disclosed embodiment includes a plurality of spaced annular ribs172 which sealingly engage the internal surface 124 of the tubularbarrel 122 as shown. The most preferred embodiments of the third stopper170 shown in FIGS. 4 to 11 and the embodiments described in theremaining figures include a longitudinal projection or stalk 174preferably having a diameter substantially less than the diameter of thebody portion of the third stopper 170 as shown. A first chamber 142 isthus defined in the tubular barrel 122 between the first and secondstoppers 132 and 134 and a second chamber 144 is defined between thesecond stopper 134 and the third stopper 170 as shown in FIG. 4. Thefirst chamber 142 is at least partially filled with a fluid, such as aliquid medical substance, diluent, solvent, or a delivery gas, and thesecond chamber 144 may be partially filled with a substance, such as aliquid, or a powder or lyophilized medical substance. The proportions ofthe chambers 142 and 144 will depend on the substances in the chambersand the particular application.

The spray nozzle and cap assembly 146 includes a cup-shaped cap 148described further below in regard to FIG. 11 and a spray nozzle body 150described further below in regard to FIG. 10. As best shown in FIG. 11,the cup-shaped cap 148 includes a tubular portion 175 including aplurality of spaced discontinuous internal annular ribs 176 extendingtransverse to the longitudinal axis of the cap 148 and an enclosed endportion 178. The end surface 181 may also include a plurality of spacedprotuberances 177 at the open end to assure purging of air from the capas described below. The spray nozzle 150 best shown in FIG. 10 includesa tubular body portion 180, open end 179, an internal surface includinga plurality of internal ribs 182, a radial flange portion 183 and atleast one longitudinal groove or passage 184 extending from the internalflange portion 183 a to the closed end 152 having a spray nozzle port154 which may be coincident with the longitudinal axis of the tubularbody portion 180 and the longitudinal axis of the tubular barrel 122 asshown. The generally longitudinal passage 184 further includes agenerally radial component (with respect to the longitudinal axis) 184 ato the spray port 154. Alternatively, the passages 184 and 184 a may bereplaced with ribs. The spray nozzle further includes a central recessor opening 185 configured to receive the longitudinal projection orcylindrical stalk 174 of the third stopper 170. It should also be notedthat the diameter of the internal surface 180 of the spray nozzle 150 inthis embodiment is preferably equal to the internal diameter of thecylindrical internal surface 124 of the tubular barrel 122 and coaxiallyaligned therewith as best shown in FIGS. 4 to 6. Alternatively, asdiscussed below, the internal diameter of the internal surface 180 maybe greater than the internal diameter of the barrel, such that theinternal “passage” surrounds the stopper 134.

FIG. 9 illustrates the assembly of the spray device 120 illustrated inFIGS. 4 to 6. One advantage of the tubular barrel 122 including an opendistal end 128 having the same internal diameter as the cylindricalinternal surface 124 (see FIGS. 4 to 6) is that the fluid and substancein the chambers 142 and 144 may be loaded from opposite ends of thetubular barrel, thereby minimizing the risk of crosscontamination of themedical substance and fluid. Thus, the second stopper 134 is firstassembled in the tubular barrel 122 adjacent to the bypass 130 as shownin FIG. 4. The fluid may then be received in the chamber 142 (see FIGS.4 to 6) and the first stopper is then inserted into the open proximalend 129 as best shown in FIG. 4. The substance may then be received inthe open distal end 128 and the third stopper 170 is then received inthe open distal end 128 forming the second chamber 144. As set forthabove, the substance in the second chamber 144 may include a liquid, apowder or a lyophilized substance. The distal end of the tubular barrel122 includes an external rib 187 as shown in FIGS. 4 to 6 and 9 whichreceives the internal ribs 182 of the spray nozzle 150 as shown in FIGS.4 to 6 until the internal flange portion 183 a engages the distal end ofthe tubular barrel. Alternatively, the ribs 182 may be replaced with aninternal thread or the parts may be otherwise secured. The cup-shapedcap 148 may then be received over the distal end 152 of the spray nozzleor preassembled on the spray nozzle as shown in FIGS. 4 to 6. Theembodiment of the spray device 120 is then ready for activation and use.

Having described the components of the embodiment of the spray device120 shown in FIGS. 4 to 11 and its assembly, it is now possible todescribe the operation of the spray device during use. First, the firststopper 132 is driven toward the second stopper 134 such as by operationof the plunger 138 as described above in regard to the spray device 20shown in FIGS. 1 to 3. This movement of the first stopper 132 toward thesecond stopper 134 as shown by arrow 162 in FIG. 5 drives the fluid inthe first chamber 142 against the second stopper 134, which drives thesecond stopper into the barrel opposite the bypass 130 as shown in FIG.5, wherein the fluid in the first chamber 142 flows through the channel131 in the bypass to mix with the substance in the second chamber 144 asshown by arrow 164. As the second chamber 144 fills with fluid, thethird stopper 170 moves toward the nozzle body 150 providing space forthe mixture and assuring complete mixing, which is a unique feature ofthe spray device 120 of this invention and the embodiments shown in theremaining figures as described below. During movement of the thirdstopper 170 into the nozzle body 150, air entrapped between the thirdstopper and the nozzle 150 escapes through the longitudinal passage 184and is purged from the nozzle through the discontinuous ribs 176 shownin FIG. 11 as shown by arrows 188 in FIG. 5. The cap 148 is then removedand the spray device is ready for spray application to a patient.Alternatively, the cap 148 may be removed prior to actuation of thespray device particularly where the cap does not include venting means.

As will be understood from the description above of the operation of thespray device 20 shown in FIGS. 1 to 3, mixing of the fluid in chamber142 with the substance in the chamber 144 is complete when the firststopper 132 engages the second stopper 134 as shown in FIG. 6. Thespacing between the second stopper 134 and the third stopper 170 willdepend upon the volume of the substance in the second chamber 144 wherethe substance is a liquid or gas. Alternatively, where the substance inthe second chamber 144 is a dry or lyophilized powder, the spacing willbe adjusted dependent upon the volume of powder and the spacingnecessary for thorough mixing. As the volume of fluid in chamber 144increases, the third stopper 170 is moved toward the nozzle 150 (whichis to the left in the Figures), the air between the third stopper 170and the spray port 154 is purged around the discontinuous ribs 176 andthe protuberances 177 best shown in FIG. 11 until the cylindricalprojection 174 is fully received in the configured opening 185 as shownin FIG. 6. In the most preferred embodiment, to prevent the mixture inthe second chamber 144 from flowing through the spray nozzle port 154until mixing is complete, the longitudinal length “L” of the thirdstopper 170 including the body portion and the cylindrical stalk 174 isslightly greater than the longitudinal length of the internal surface ofthe nozzle body 150 measured from the interior surface 152 a of the endportion 152 of the nozzle to the abutment surface 183 a of the radialflange 183 which engages the distal end 128 of the tubular barrel asshown in FIG. 10. Thus, the mixture in the second chamber 144 isprevented from flowing from the spray nozzle port 154 until the bodyportion of the third stopper 170 is moved fully into the spray nozzle.

Finally, after complete mixing of the fluid and substance in the secondchamber 144 and driving of the first stopper 132 against the secondstopper 134 as shown in FIG. 6, the stalk portion 174 of the thirdstopper 170 is driven against the opposed surface 152 a of the endportion 152 which also defines the end wall of the central recess 185.Compression of the stalk portion 174 against the face 152 a deforms thestalk 174 as shown in FIG. 7, such that the body portion of the thirdstopper 170 is fully received in the cylindrical passage 186 in thenozzle 150 as shown in FIG. 7, wherein the fluid in the second chamber144 is in fluid communication with the spray nozzle port 154 throughgenerally longitudinal passages 184 and 184 a shown in FIG. 10 whichcontinues through the surface 152 a as shown. The mixture in chamber 144then flows under pressure through the longitudinal channel 184 and 184 ato the nozzle port 154, generating a fine spray or mist of fluid 168 asshown in FIG. 7. As set forth above, the third stopper 170 including theintegral stalk portion 174 is preferably formed of a resilient ordeformable material, such as natural or synthetic rubber, but may alsobe formed of a resilient polymer. Alternatively, the stalk portion 174may be formed of a resilient material different from the body portion ofthe third stopper 170 or the end of the third stopper 170 including thestalk portion 174 may be separate from the body portion as describedbelow in regard to the embodiments of the spray device disclosed inFIGS. 12 to 15. Finally, when the second stopper 134 engages the thirdstopper 170 as shown in FIG. 8, the second chamber 144 shown in FIG. 7is virtually empty. As will be understood by those skilled in this art,the spray devices of this invention may be utilized for a single doseapplication or multiple doses, wherein the tubular barrel 122 may bemarked with suitable indicia for each dose and the tubular barrel ispreferably formed of glass or clear plastic to permit visualization ofthe mixing of the fluid and substance and volume of the mixtureremaining in the second chamber 144.

FIGS. 12 to 14 illustrate further embodiments of the spray device ofthis invention wherein the third stopper is comprised of two separatecomponents which provide fluid communication through the third stopper.In the embodiment of the spray device 220 shown in FIGS. 12 and 13, thetubular barrel 222 and the first and second stoppers may be identical tothe spray device 120 disclosed in FIGS. 4 to 11 described above. Onlythe leading portion of the second stopper 234 is shown in FIGS. 12 and13 as required for a full description of this embodiment. The spraynozzle 250 may be identical to the spray nozzle 150 described above,except that the longitudinal channel 184 is not required or necessary,but the transverse channel 184 a in surface 152 a is required unless theend of the stalk 174 includes a radial groove. No further description ofthe spray nozzle 250 is therefore required and the elements of the spraynozzle are numbered in the same sequence as the spray nozzle 150described above. In this embodiment of the spray device 220, the thirdstopper is comprised of a body portion 290 which sealingly engages theinternal surface 224 of the tubular barrel 222 having a reducedthickness axial portion or septum 291 and an end part 292 which includesthe cylindrical axial projection or stalk 274. The end part 292 ispreferably formed of a hard plastic and the projecting axial stalkportion 274 may be initially received in the central axial opening 285as shown. The end part 292 further includes an axially projectingpiercing element 293 which may be integral with the end part 292 havinga sharp end 294 extending opposite the stalk portion 274 toward theseptum 291 of the body portion 290 as shown in FIG. 12. The piercingelement 293 may be cylindrical and includes an axial passage 295 whichcommunicates with the radial passage 296 in the end part 292 as shown inFIGS. 12 and 13. The interior surface 252 a of the end portion 252 ofthe nozzle member 250 may include a radial groove shown in surface 152 ain FIG. 10 or the end of the stalk 274 may include a radial groove toprovide fluid communication to the spray nozzle port 254.

The actuation of the spray device 220 shown in FIGS. 12 and 13 may thenbe described, as follows. As described above, the initial actuation ofthe spray device 220 is identical to the spray device 120 describedabove, wherein the first stopper (not shown) is driven toward the secondstopper 234 to mix the fluid and substance in the second chamber 244.Movement of the second stopper 234 then drives the body portion 290 ofthe second stopper assembly into the cylindrical internal surface 286 ofthe nozzle member drives the sharp end 294 of the piercing element 293through the reduced thickness axial portion or septum 291 of the bodyportion 290 to pierce the septum 291 as shown in FIG. 13 andestablishing communication through the axial and radial passages 295 and296, respectively to the spray nozzle port 254, resulting in a finespray or mist 268 as shown in FIG. 13. As will be understood, the fluidand substance in the chamber 244 will be thoroughly mixed andpressurized by the second stopper 234 prior to piercing of the septum291 to establish a spray 268 as described above in regard to theembodiment of the spray device 120.

The actuation and operation of the spray device 320 shown in FIGS. 14and 15 is similar to the operation of the spray device 220 shown inFIGS. 12 and 13 in that the third stopper is comprised of two separatecomponents which cooperate to establish communication through thestopper assembly. In the embodiment of the spray device 320 shown inFIGS. 14 and 15, the third stopper assembly is comprised of a bodyportion 390 and a separate end part 392 having an integral stalk portion374 which may be initially received in the central opening 385 of thenozzle member 350 as shown. The nozzle member 350 may be identical tothe nozzle member 250 described above in regard to FIGS. 12 and 13 andhas been numbered in the same sequence. Therefore no further descriptionof the nozzle member 350 is required. In this embodiment, the bodyportion 390 of the third stopper includes an axial passage 391 sealedwith a ball 397 or other suitable removable sealing element. Asdescribed above, the body portion 390 of the third stopper is preferablyformed of a resilient material, such as natural or synthetic rubber orresilient plastic, and the ball 397 may be hollow and formed of asuitable polymer, metal, glass or the like. The end part 392 of thethird stopper assembly includes an axially projecting stalk portionwhich may be initially received in the central opening 385 of the nozzlemember 350 and the body portion 390 is initially spaced from the endpart 392 in sealed relation with the cylindrical internal surface 324 ofthe tubular barrel 322 as described above in regard to FIGS. 12 and 13.The end part 392 further includes a bifurcated driver element or portion393 extending axially opposite the cylindrical projection 374 configuredto be received in the axially passage 391 in the body portion 390. Theslot or space 394 between the bifurcated driver portions 393 extendsthrough the end part 292 as shown in FIG. 14, such that fluidcommunication is provided through the end part 392 as shown.Alternatively, end part 392 could be tubular or solid and the conicalportion could include a passage.

The actuation of the spray device 320 shown in FIGS. 14 and 15 issimilar to the embodiment of the spray device 220 described above withreference to FIGS. 12 and 13. As described above, the spray device 320includes a tubular barrel 322 having a bypass as shown in FIGS. 4 to 6(not shown in FIGS. 14 and 15) and a first and second stopper spaced asdescribed above. FIGS. 14 and 15 illustrate only the second stopper 334.During actuation, the first stopper (not shown) is driven toward thesecond stopper 334, and the fluid in the first chamber drives the secondstopper 334 into the barrel adjacent the bypass (not shown), driving thefluid in the first chamber into the second chamber 344. Continuedmovement of the first stopper against the second stopper 334 drives thebody portion 390 of the third stopper assembly into the cylindricalinternal surface 324 of the nozzle member, which drives the driverportion 393 of the end part 392 into the passage 391 of the body portion390. The driver portion 393 then drives the ball 397 out of the passage391 as shown in FIG. 15, establishing fluid communication between thesecond chamber 344 and the spray nozzle port 354 through the passage394, generating a spray 368 as described above.

The actuation of the embodiment of the spray device 420 shown in FIGS.16 and 17 is similar to the embodiment of the spray device 120 shown inFIGS. 4 to 11 described above. In this embodiment, the third stopper 470includes an integral axial projection or stalk portion 474 similar tothe third stopper 170 described above, except that the stalk portion 474further includes a reduced diameter neck portion 490 as shown in FIG.16. The nozzle member 450 may be identical to the nozzle member 150described above, except that the central opening 485 includes an annularrib 491 adjacent the opening to the central opening 485 as shown in FIG.16. It should also be noted that the inner wall of the central opening485 is preferably slightly conical as shown in FIG. 16. The remainder ofthe spray device 420 shown in FIGS. 16 and 17 may be identical to theembodiments described above. That is, the spray device includes atubular barrel 422 having opposed open ends, first and second spacedstoppers located within the tubular barrel as described above. Further,the cylindrical surface 486 of the nozzle member 450 includes agenerally longitudinally extending groove or slot 484, such as shown at184 in FIG. 10 having a transverse groove 484 a in the surface 452 a asdescribed above. The actuation of the spray device 420 may now bedescribed as follows.

The third stopper 470 may be initially spaced from the nozzle member 450as described above in regard to the embodiment of the spray device 120shown in FIGS. 4 to 11. Alternatively, the stalk portion 474 may beinitially received in the conical central opening 485 as shown in FIG.16. When the stalk portion 474 is received in the central opening 485,the annular rib 491 seals against the external surface of the stalkportion 474 as shown in FIG. 16. Then, following mixing of the substanceand fluid in second chamber 444 and driving of the second stopper 434toward the third stopper, the stalk portion 474 is deformed axiallyagainst the internal surface 452 a of the end portion 452 as shown inFIG. 17, which reduces the axial length of the stalk portion andreceives the annular rib 491 in the reduced diameter neck portion 490 asshown in FIG. 17. Receipt of the annular rib 491 in the reduced diameterneck portion 490 establishes fluid communication through the generallyaxially extending groove shown at 484 and the groove 484 a in thetransverse surface (also shown at 152 a in FIG. 10) providing fluidcommunication between the second chamber 444 and the spray nozzle port454 as shown in FIG. 17, driving the fluid through the spray nozzle port454 and providing a fine mist 468 through the nozzle as described above.

Having described several embodiments of the spray device of thisinvention, it will be understood that various modifications may be madeto such embodiments within the purview of the appended claims. Where thefirst chamber 42, 142, etc. includes a liquid, the second chamber 44,144, etc. may include a second liquid, powder or lyophilized medicamentfor example. Alternatively, the first chamber may include a carrier gas,such as compressed air for example, and the second chamber may include apowder or lyophilized medicament, such that the spray device of thisinvention may be used to deliver a spray of powder or lyophilizedmedicament to the respiratory system of a patient through the nose ormouth. Although a gas is compressible, sufficient pressure may begenerated in the first chamber by the first stopper to deliver the gasthrough the bypass to aerosolize the powder for delivery to a patient.For example, various spray nozzles may be utilized with the dual chamberspray device of this invention. In the preferred embodiments, thetubular barrel has a substantially constant diameter to permit fillingor loading of the spray device from the opposed ends to avoidcrosscontamination of the fluid and substance as described above. As setforth above, the terms “substance” and “medical substance” are intendedto broadly cover any drug, vaccine or medicament which may be applied inthe form of a spray to a patient. The cap 148 having spaced internalribs 176 as shown in FIG. 11 may be utilized with any of the disclosedembodiments of the spray device of this invention including FIGS. 1 to 3to permit purging of air between the third stopper and the spray nozzleport as described above. Alternatively, the cap may be a conventionalcup-shaped cap, wherein the cap is removed prior to actuation. Thebypass 30, 130, etc. may also take various forms other than theoutwardly bulging semicircular passage shown. For example, the bypassmay comprise a plurality of outwardly bulging semicircular passages orthe bypass may comprise one or a plurality of inwardly projecting ribswhich engage the resilient second stopper providing an internal passageor passages permitting the flow of fluid past the second stopper whenthe second stopper is located opposite the inwardly projecting portionsof the barrel.

Further, in the preferred embodiments of the spray device, wherein thenozzle member includes a generally longitudinally extending internalgroove 184, 184 a, the internal diameter 186 is preferably generallyequal to the internal diameter 124 of the barrel as shown. However, theinternal diameter of the spray nozzle may be substantially greater thanthe internal diameter of the barrel, eliminating the requirement for thelongitudinal portion 184 of the internal passage, wherein the mixedfluid and substance flows around the third stopper when the thirdstopper is located within the nozzle body. In this embodiment, theprojecting stalk portion 174 is received in the central opening 185during actuation of the spray device and, upon axial deformation of thestalk portion, the body portion of the third stopper is received withinthe larger diameter internal surface of the spray nozzle, permitting themixed fluid and substance to flow around the body portion of the thirdstopper into the spray nozzle port through the passage 184 a asdescribed above. As used herein, the term “generally longitudinalpassage” would then include the annular passage around the body portionof the third stopper. Alternatively, the tubular barrel of the spraydevice may include a longitudinal groove or rib on the inside surfaceextending from the distal end and providing fluid communication to thenozzle port. In this embodiment, the third stopper does not have to bereceived within the body of the nozzle and the nozzle may be secured tothe end of the barrel. The longitudinal groove would preferably have alength generally equal to the body portion of the third stopper for thereasons stated above. Where a removable sealing member is provided in apassage through the third stopper 390 as shown at 397 in FIGS. 14 and15, the removable sealing member 397 may take any shape and maybecaptured in an opening in the second stopper to reduce the dead volumeof the mixture upon completion of the spray sequence. The embodiments ofthe spray device disclosed herein provide for thorough mixing of afluid, such as liquid medical substance, diluent or solvent and aliquid, lyophilized or powder medical substance without the requirementof a hypodermic syringe having a sharp needle cannula and a vial havinga pierceable stopper and an aluminum cap as set forth above. The tubularbarrel may be formed of glass or a clear polymer, permittingvisualization of the mixing of the fluid and substance and to providefor one or multiple doses as described. The invention is now claimed, asfollows.

1. A spray device, comprising: a tubular barrel having an internalsurface, opposed first and second open ends and a bypass between saidfirst and second open ends, a spray nozzle member on said second openend of said tubular barrel including an internal surface and a sprayport, first, second and third stoppers located within said tubularbarrel each having an external surface engaging said internal surface ofsaid tubular barrel and moveable in said tubular barrel, said firststopper initially located adjacent said first open end of said tubularbarrel, said second stopper spaced from said first stopper and initiallylocated between said first stopper and said bypass of said tubularbarrel and said third stopper having a body portion located between saidbypass and said second open end of said tubular barrel, a fluid locatedbetween said first and second stoppers and a substance located betweensaid second and third stoppers, wherein said third stopper includes alongitudinal projection and said spray nozzle includes a recesscoaxially aligned with said spray port configured to receive saidlongitudinal projection, whereby movement of said first stopper towardsaid second open end of said tubular barrel moves said second stopper toadjacent said bypass causing said fluid to flow between said first andsecond stoppers through said bypass, mixing said fluid between saidfirst and second stoppers with said substance between said second andthird stoppers, continued movement of said first stopper then drivessaid first stopper against said second stopper and continued movement ofsaid first and second stoppers drives said third stopper toward saidspray nozzle member said longitudinal projection is deformable againstan internal surface of said recess, whereby movement of said thirdstopper receives said longitudinal projection in said recess in saidspray nozzle member and continued movement of said third stopper axiallycompresses said longitudinal projection providing fluid communicationbetween said tubular barrel and said spray port through an internalpassage creating a spray of said mixture for delivery of said mixture toa patient.
 2. The spray device as defined in claim 1, wherein saidinternal surface of said spray nozzle member includes a generallylongitudinal internal passage providing fluid communication between saidtubular barrel and said spray port of said spray nozzle member only whensaid third stopper is located in said spray nozzle member.
 3. The spraydevice as defined in claim 1, wherein said third stopper has alongitudinal length greater than the longitudinal length of saidinternal surface of said spray nozzle member and said longitudinalprojection is compressible, whereby compression of said longitudinalprojection drives said third stopper within said spray nozzle memberproviding fluid communication between said tubular barrel and said sprayport through said internal passage.
 4. The spray device as defined inclaim 1 wherein said longitudinal projection is deformable and includesa reduced diameter neck portion and said recess includes a radiallyprojecting annular rib adjacent an open end of said recess, wherebymovement of said third stopper deforms said longitudinal projection,receiving said internal radial rib into said reduced diameter neckportion establishing fluid communication between said tubular barrel andsaid spray port of said spray nozzle member.
 5. The spray device asdefined in claim 2, wherein said body portion of said third stopperincludes an external surface engaging said internal surface of saidtubular barrel and a separate end portion including a projecting portionhaving a diameter less than said body portion of said third stopperreceived in an opening of said spray nozzle coaxially aligned with saidspray port configured to receive said projecting portion, wherein saidbody portion of said third stopper is initially spaced from said endportion, whereby movement of said body portion of said third stopperinto engagement with said end portion receives said body portion in saidspray nozzle member establishing fluid communication between saidtubular barrel and said spray port through an internal passage.
 6. Thespray device as defined in claim 5, wherein said body portion of saidthird stopper includes a passage therethrough and a movable sealingelement in said passage, and said end portion of said third stopperincludes a projecting driver portion configured to be received in saidpassage, whereby movement of said body portion of said third stoppertoward said end portion drives said driver portion through said passage,moving said removable sealing member and providing fluid communicationthrough said passage.
 7. The spray device as defined in claim 5, whereinsaid body portion of said third stopper includes a pierceable septum andsaid end portion includes a projecting piercing element projectingtoward said septum, whereby movement of said body portion of said thirdstopper toward said end portion drives said projecting piercing elementthrough said septum providing fluid communication through said bodyportion with said spray port.